Effect of aging on the human myometrium at single-cell resolution.

Age-associated myometrial dysfunction can prompt complications during pregnancy and labor, which is one of the factors contributing to the 7.8-fold increase in maternal mortality in women over 40. Using single-cell/single-nucleus RNA sequencing and spatial transcriptomics, we have constructed a cellular atlas of the aging myometrium from 186,120 cells across twenty perimenopausal and postmenopausal women. We identify 23 myometrial cell subpopulations, including contractile and venous capillary cells as well as immune-modulated fibroblasts. Myometrial aging leads to fewer contractile capillary cells, a reduced level of ion channel expression in smooth muscle cells, and impaired gene expression in endothelial, smooth muscle, fibroblast, perivascular, and immune cells. We observe altered myometrial cell-to-cell communication as an aging hallmark, which associated with the loss of 25 signaling pathways, including those related to angiogenesis, tissue repair, contractility, immunity, and nervous system regulation. These insights may contribute to a better understanding of the complications faced by older individuals during pregnancy and labor.

The role of microRNAs in understanding sex-based differences in Alzheimer's disease.

BACKGROUND: The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment. METHODS: A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms. RESULTS: Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process. CONCLUSIONS: Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.

Alzheimer's disease (AD)­a neurodegenerative disease mainly affecting older patients­is characterized by cognitive deterioration, memory loss, and progressive incapacitation in daily activities. While AD affects almost twice as many females as males, and cognitive deterioration and brain atrophy develop more rapidly in females, the biological causes of these differences remain poorly understood. MicroRNAs (miRNAs) regulate gene expression and impact a wide variety of biological processes; therefore, studying the differential expression of miRNAs in female and male AD patients could contribute to a better understanding of the disease. We reviewed studies of miRNA expression in female and male AD patients and integrated results using a meta-analysis methodology and then identified those genes regulated by the altered miRNAs to establish an association with biological processes. We found 16 (females) and 22 (males) miRNAs altered in the blood of AD patients. Functional enrichment revealed sex-based differences in the affected altered biological processes­protein modification and degradation and cell death in male AD patients and RNA processing in female AD patients. A similar analysis in the brains of AD patients revealed six (females) and four (males) miRNAs with altered expression; however, our analysis failed to highlight any specifically altered biological processes. Overall, we highlight the sex-based differential expression of miRNAs (and biological processes affected) in the blood and brain of AD patients.

A cell abundance analysis based on efficient PAM clustering for a better understanding of the dynamics of endometrial remodelling.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) is a powerful tool for investigating cell abundance changes during tissue regeneration and remodeling processes. Differential cell abundance supports the initial clustering of all cells; then, the number of cells per cluster and sample are evaluated, and the dependence of these counts concerning the phenotypic covariates of the samples is studied. Analysis heavily depends on the clustering method. Partitioning Around Medoids (PAM or k-medoids) represents a well-established clustering procedure that leverages the downstream interpretation of clusters by pinpointing real individuals in the dataset as cluster centers (medoids) without reducing dimensions. Of note, PAM suffers from high computational costs and memory requirements. RESULTS: This paper proposes a method for differential abundance analysis using PAM as a clustering method and negative binomial regression as a statistical model to relate covariates to cluster/cell counts. We used this approach to study the differential cell abundance of human endometrial cell types throughout the natural secretory phase of the menstrual cycle. We developed a new R package -scellpam-, that incorporates an efficient parallel C++ implementation of PAM, and applied this package in this study. We compared the PAM-BS clustering method with other methods and evaluated both the computational aspects of its implementation and the quality of the classifications obtained using distinct published datasets with known subpopulations that demonstrate promising results. CONCLUSIONS: The implementation of PAM-BS, included in the scellpam package, exhibits robust performance in terms of speed and memory usage compared to other related methods. PAM allowed quick and robust clustering of sets of cells with a size ranging from 70,000 to 300,000 cells. https://cran.r-project.org/web/packages/scellpam/index.html . Finally, our approach provides important new insights into the transient subpopulations associated with the fertile time frame when applied to the study of changes in the human endometrium during the secretory phase of the menstrual cycle.

Decoding the endometrial niche of Asherman's Syndrome at single-cell resolution.

Asherman's Syndrome is characterized by intrauterine adhesions or scarring, which cause infertility, menstrual abnormalities, and recurrent pregnancy loss. The pathophysiology of this syndrome remains unknown, with treatment restricted to recurrent surgical removal of intrauterine scarring, which has limited success. Here, we decode the Asherman's Syndrome endometrial cell niche by analyzing data from over 200,000 cells with single-cell RNA-sequencing in patients with this condition and through in vitro analyses of Asherman's Syndrome patient-derived endometrial organoids. Our endometrial atlas highlights the loss of the endometrial epithelium, alterations to epithelial differentiation signaling pathways such as Wnt and Notch, and the appearance of characteristic epithelium expressing secretory leukocyte protease inhibitor during the window of implantation. We describe syndrome-associated alterations in cell-to-cell communication and gene expression profiles that support a dysfunctional pro-fibrotic, pro-inflammatory, and anti-angiogenic environment.

The human periconceptional maternal-embryonic space in health and disease.

Pregnancy is established during the periconceptional period as a continuum beginning with blastocyst attachment to the endometrial epithelial surface followed by embryo invasion and placenta formation. This period sets the foundation for the child and mother's health during pregnancy. Emerging evidence indicates that prevention of downstream pathologies in both the embryo/newborn and pregnant mother may be possible at this stage. In this review, we discuss current advances in the periconceptional space, including the preimplantation human embryo and maternal endometrium. We also discuss the role of the maternal decidua, the periconceptional maternal-embryonic interface, the dialogue between these elements, and the importance of the endometrial microbiome in the implantation process and pregnancy. Finally, we discuss the myometrium in the periconceptional space and review its role in determining pregnancy health.

Aberrant Alternative Splicing in U2af1/Tet2 Double Mutant Mice Contributes to Major Hematological Phenotypes.

Mutations in splicing factors are recurrent somatic alterations identified in myelodysplastic syndromes (MDS) and they frequently coincide with mutations in epigenetic factors. About 25% of patients present concurrent mutations in such pathways, suggesting a cooperative role in the pathogenesis of MDS. We focused on the splicing factor U2AF1 involved in the recognition of the 3' splice site during pre-mRNA splicing. Using a CRISPR/Cas9 system, we created heterozygous mice with a carboxy-terminal truncated U2af1 allele (U2af1mut/+), studied the U2af1mut/+ hematopoietic system, and did not observe any gross differences in both young (12-13 weeks) and old (23 months) U2af1mut/+ mice, except for a reduction in size of approximately 20%. However, hematopoietic stem/progenitor cells lacked reconstitution capacity in transplantation assays and displayed an aberrant RNA splicing by RNA sequencing. We also evaluated U2af1mut/+ in conjunction with Tet2-deficiency. Novel double mutant U2af1mut/+Tet2-/- mice showed increased monogranulocytic precursors. Hematopoietic stem/progenitor cells were also enhanced and presented functional and transcriptomic alterations. Nonetheless, U2af1mut/+Tet2-/- mice did not succumb to MDS disease over a 6-month observation period. Collectively, our data suggest that cooperation between mutant U2af1 and Tet2 loss is not sufficient for MDS initiation in mice.

Cost-minimization analysis favors outpatient quick diagnosis unit over hospitalization for the diagnosis of potentially serious diseases.

BACKGROUND: Quick diagnosis units (QDUs) are a promising alternative to conventional hospitalization for the diagnosis of suspected serious diseases, most commonly cancer and severe anemia. Although QDUs are as effective as hospitalization in reaching a timely diagnosis, a full economic evaluation comparing both approaches has not been reported. AIMS: To evaluate the costs of QDU vs. conventional hospitalization for the diagnosis of cancer and anemia using a cost-minimization analysis on the proven assumption that health outcomes of both approaches were equivalent. METHODS: Patients referred to the QDU of Bellvitge University Hospital of Barcelona over 51 months with a final diagnosis of severe anemia (unrelated to malignancy), lymphoma, and lung cancer were compared with patients hospitalized for workup with the same diagnoses. The total cost per patient until diagnosis was analyzed. Direct and non-direct costs of QDU and hospitalization were compared. RESULTS: Time to diagnosis in QDU patients (n=195) and length-of-stay in hospitalized patients (n=237) were equivalent. There were considerable costs savings from hospitalization. Highest savings for the three groups were related to fixed direct costs of hospital stays (66% of total savings). Savings related to fixed non-direct costs of structural and general functioning were 33% of total savings. Savings related to variable direct costs of investigations were 1% of total savings. Overall savings from hospitalization of all patients were €867,719.31. CONCLUSION: QDUs appear to be a cost-effective resource for avoiding unnecessary hospitalization in patients with anemia and cancer. Internists, hospital executives, and healthcare authorities should consider establishing this model elsewhere.

Microvesicles from Mesenchymal Stromal Cells Are Involved in HPC-Microenvironment Crosstalk in Myelodysplastic Patients.

Exosomes/microvesicles (MVs) provide a mechanism of intercellular communication. Our hypothesis was that mesenchymal stromal cells (MSC) from myelodysplastic syndrome (MDS) patients could modify CD34+ cells properties by MVs. They were isolated from MSC from MDS patients and healthy donors (HD). MVs from 30 low-risk MDS patients and 27 HD were purified by ExoQuick-TC™ or ultracentrifugation and identified by transmission electron microscopy, flow cytometry (FC) and western blot for CD63. Incorporation of MVs into CD34+ cells was analyzed by FC, and confocal and fluorescence microscopy. Changes in hematopoietic progenitor cell (HPC) properties were assessed from modifications in microRNAs and gene expression in CD34+ cells as well as viability and clonogenic assays of CD34+ cells after MVs incorporation. Some microRNAs were overexpressed in MVs from patients MSC and two of them, miR-10a and miR-15a, were confirmed by RT-PCR. These microRNAs were transferred to CD34+ cells, modifying the expression of MDM2 and P53 genes, which was evaluated by RT-PCR and western blot. Finally, examining CD34+ cells properties after incorporation, higher cell viability (p = 0.025) and clonogenic capacity (p = 0.037) were observed when MVs from MDS patients were incorporated. In summary, we show that BM-MSC release MVs with a different cargo in MDS patients compared with HD. These structures are incorporated into HPC and modify their properties.

Prevalence, Clinical Characteristics, and Risk Factors for Non-recording of Alcohol Use in Hospitals across Europe: The ALCHIMIE Study.

AIM: To determine the detection rates, clinical features, and risk factors for lack of registration of alcohol use in medical patients admitted in European hospitals. METHODS: A point-prevalence, cross-sectional, multicenter survey involving 2100 medical inpatients from 43 hospitals from 8 European countries. Patients were screened for current alcohol use, using standardized questionnaires. Alcohol use recording in medical records was assessed. RESULTS: Of the 2100, more than a half reported alcohol use. Significant differences were shown in the prevalence of drinking and the recording rates of alcohol use among the hospitals and countries involved. Overall, 346 patients (16%) fulfilled criteria for alcohol use disorder. Alcohol use was registered in 909 (43%) of medical records, with quantification in 143 (7%). Multivariate analysis showed that women (OR 1.49), older age patients (OR 1.23), patients from the Northern European countries (OR 4.79) and from hospitals with high local alcohol prevalence (OR 1.59) were more likely to have lack of alcohol use registration in their medical files. CONCLUSIONS: A considerable proportion of medical patients admitted in European hospitals fulfill criteria for alcohol use disorders. These patients are frequently overlooked during hospitalization and not appropriately registered in medical records. Women, older patients, and inpatients from European areas with high local alcohol use prevalence are at higher risk associated with a non-recording of alcohol use.

Coinfection with "Rickettsia sibirica subsp. mongolotimonae" and Rickettsia conorii in a Human Patient: a Challenge for Molecular Diagnosis Tools.

Rickettsioses are zoonoses transmitted by vectors. More than one agent can coexist in vectors. Although vectors may transmit more than one microorganism to humans, information on dual infections is scarce. We present a case of a patient with an atypical rickettsiosis diagnosis in whom two species of Rickettsia were detected.

A quick diagnosis unit as an alternative to conventional hospitalization in a tertiary public hospital: a descriptive study.

INTRODUCTION:  Reports indicate that a significant number of patients admitted to internal medicine units could be studied on an outpatient basis. OBJECTIVES:  This article assesses a quick diagnosis unit (QDU) as an alternative to acute hospitalization for the diagnostic study of patients with potentially serious diseases and suspected malignancy.  PATIENTS AND METHODS:  Between March 2008 and June 2012, 1226 patients were attended by the QDU. Patients were referred from the emergency department, primary health care centers, and outpatient clinics according to well­defined criteria. Clinical information was prospectively registered in a database.  RESULTS:  There were 634 men (51.7%), with a mean age of 60.5 ±17.5 years. The mean time to the first visit was 3.5 ±5.3 days. Most patients (65.7%) required only 2 visits. The mean interval to diagnosis was 12.2 ±14.7 days. A total of 324 patients (26.4%) had cancer. The diagnosis was  solid tumor in 81.5% of the cases, lymphoma in 19.8%, and various hematologic malignancies in 4.3%. The second most common diagnosis was anemia not associated with cancer (8.6% of the cases). Admission to the QDU allowed to avoid conventional hospitalization for diagnostic studies in 71.5% of the patients, representing a mean freeing­up rate of 7 internal medicine beds per day. In a satisfaction survey, 97% of the patients were completely or very satisfied and 96% preferred the QDU to conventional hospitalization.  CONCLUSIONS:  A QDU may be a feasible alternative to conventional hospitalization for the diagnosis of otherwise healthy patients with suspected severe disease. Appropriately managed and supported, QDUs can lighten the burden of emergency departments and reduce the need for hospitals beds.

Aspiration pneumonia in old patients with dementia. Prognostic factors of mortality.

BACKGROUND: Prognostic factors of mortality in elderly patients with dementia with aspiration pneumonia (AP) are scarcely known. We determined the mortality rate and prognostic factors in old patients with dementia hospitalized due to AP. METHODS: We prospectively studied 120 consecutive patients aged ≥ 75 years with dementia admitted with AP to two tertiary university hospitals. We collected data on demographic and clinical variables and comorbidities. Oropharyngeal swallowing was assessed by the water swallow test. RESULTS: Sixty-one (50.8%) patients were female, and mean age was 86 ± 9 years. The swallow test was performed in 68 patients, revealing aspiration in 92.6%. Patients with repeat AP (28.3%) were more-frequently taking thickeners (61.8% vs.11.6%, p<0.0001) and were less-frequently prescribed angiotensin-converting-enzyme (ACE) inhibitors (8.8% vs. 27.9%, p<0.001) than patients with a first episode. Hospital mortality was 33.3%; these patients had lower lymphocyte counts and higher percentage of multilobar involvement. In the multivariate model, involvement of ≥ 2 pulmonary lobes was associated with hospital mortality (OR 3.051, 95% CI 1.248 to 7.458, p<0.01). Six-month mortality was 50.8%; these patients were older and had worse functional capacity and laboratory data indicative of malnutrition. In the multivariate model, lower albumin levels were associated with six-month mortality (OR 1.129, 95% CI 1.008 to 1.265, p<0.03). CONCLUSION: In-hospital and 6-month mortality were high (one-third and one-half patients, respectively). Multilobar involvement and lower lymphocyte counts were associated with hospital mortality, and older age, greater dependence and malnutrition with six-month mortality.

Geriatric assessment and chronic kidney disease in the oldest old: the Octabaix study.

BACKGROUND: The prevalence of chronic kidney disease (CKD) in older people is increasing. We determine the proportion of CKD in a sample of 321, 85-year-old community-dwelling subjects, and assess the association of socio-demographic data, global geriatric assessment data and comorbidity with CKD according to the estimated glomerular filtration rate (eGFR) of subjects. METHODS: Serum creatinine, eGFR (derived in ml/min/1.73 m(2) using the Modification of Diet in Renal Disease formula), socio-demographic variables, the Barthel Index (BI), the Spanish version of the Mini-Mental State Examination (MEC), the Mini Nutritional Assessment (MNA), the Charlson Index, the Gait Rating Scale, social risk, quality of life and prevalent chronic diseases were collected. RESULTS: CKD prevalence was 56.7% for eGFR < 60 ml/min/1.73 m(2), 19.9% for eGFR < 45 ml/min/1.73 m(2) and 6.6% for GFR < 30 ml/min/1.73 m(2). Multiple logistic regression analysis showed that a prior diagnosis of hypertension was associated with an eGFR < 60 ml/min/1.73 m(2) (p<0.008, OR 2.134, 95% CI 1.216-3.744). A diagnosis of heart failure (p<0.001, OR 3.610, 95% CI 1.677-7.771) and a poor score on the quality of life measure (p<0.008, OR 0.9660, 95% CI 0.966-0.995) were associated with an eGFR < 45 ml/min/1.73 m(2). CONCLUSIONS: More than half of the oldest old in this study had an eGFR < 60 ml/min/1.73 m(2). A history of hypertension was associated with CKD. The group of patients with an eGFR < 45 ml/min/1.73 m(2) was associated with a diagnosis of heart failure and a worse quality of life.

Impaired expression of DICER, DROSHA, SBDS and some microRNAs in mesenchymal stromal cells from myelodysplastic syndrome patients.

UNLABELLED: Background Recent findings suggest that a specific deletion of Dicer1 in mesenchymal stromal cell-derived osteoprogenitors triggers several features of myelodysplastic syndrome in a murine model. Our aim was to analyze DICER1 and DROSHA gene and protein expression in mesenchymal stromal cells (the osteoblastic progenitors) obtained from bone marrow of myelodysplastic syndrome patients, in addition to microRNA expression profile and other target genes such as SBDS, a DICER1-related gene that promotes bone marrow dysfunction and myelodysplasia when repressed in a murine model. DESIGN AND METHODS: Mesenchymal stromal cells from 33 bone marrow samples were evaluated. DICER, DROSHA and SBDS gene expression levels were assessed by real-time PCR and protein expression by Western blot. MicroRNA expresion profile was analyzed by commercial low-density arrays and some of these results were confirmed by individual real-time PCR. RESULTS: Mesenchymal stromal cells from myelodysplastic syndrome patients showed lower DICER1 (0.65±0.08 vs. 1.91±0.57; P=0.011) and DROSHA (0.62±0.06 vs. 1.38±0.29; P=0.009) gene expression levels, two relevant endonucleases associated to microRNA biogenesis, in comparison to normal myelodysplastic syndrome. These findings were confirmed at protein levels by Western blot. Strikingly, no differences were observed between paired mononuclear cells from myelodysplastic syndrome and controls. In addition, mesenchymal stromal cells from myelodysplastic syndrome patients showed significant lower SBDS (0.63±0.06 vs. 1.15±0.28; P=0.021) gene expression levels than mesenchymal stromal cells from healthy controls. Furthermore, mesenchymal stromal cells from myelodysplastic syndrome patients showed an underlying microRNA repression compared to healthy controls. Real-time PCR approach confirmed that mir-155, miR-181a and miR-222 were down-expressed in mesenchymal stromal cells from myelodysplastic syndrome patients. Conclusions This is the first description of an impaired microRNA biogenesis in human mesenchymal stromal cells from myelodysplastic syndrome patients, where DICER1 and DROSHA gene and protein downregulation correlated to a gene and microRNA abnormal expression profile, validating the animal model results previously described.

Género y alteraciones hepáticas, nutricionales y metabólicas del alcoholismo grave: estudio de 480 pacientes / Gender and liver, nutritional and metabolic alterations of severe alcoholism: a study of 480 patients

Fundamento y objetivo: Analizar diferencias de género en alteraciones hepáticas, nutricionales y metabólicas asociadas al alcoholismo.Pacientes y método: Estudio transversal en pacientes ingresados para desintoxicación de alcohol entre 1999 y 2006 en dos hospitales del área de Barcelona. Durante el ingreso se evaluó la comorbilidad previa y se obtuvieron muestras de sangre para hemograma, bioquímica y serologías además de datos sociodemográficos, antropométricos y del consumo de alcohol y drogas. Resultados: 566 ingresos consecutivos en 480 pacientes (375 hombres). La edad al ingreso fue 43 años (Rango Intercuartil [RIQ]: 36,3-49,0). Globalmente, el 68,4% presentaba macrocitosis (VCM>95 fl.), 81,7% GGT>40U/L y 57,7% AST > 37U/L. En las alteraciones hepáticas, la frecuencia de fosfatasa alcalina>120 U/L fue significativamente superior en mujeres que en hombres (18,5 vs. 10,5%, p=0,037). Sin embargo, los hombres mostraban más frecuencia de hiperferritinemia (>90ng/mL) que las mujeres (85,7 vs. 62,2%) (p=0,000). La probabilidad de presentar dos o más alteraciones hepáticas fue significativamente mayor en los hombres (OR: 1,64, IC 95%: 1,01-2,65) (p=0,043). En las alteraciones nutricionales, las mujeres presentaron mayor frecuencia de macrocitosis (77,5 vs. 65,8%, p=0,026), de creatinina sérica baja (<0,7mg/100mL) (28,2 vs. 14,6%, p=0,001) y ferritina sérica baja (<30ng/mL) (10,8 vs. 3,9%, p=0,020), así como mayor probabilidad de tener múltiples alteraciones nutricionales (OR: 1,59, IC 95%: 1,02-2,48) (p=0,040). Por otro lado, los hombres presentaron mayor frecuencia de anemia (32,3 vs. 21,4%, p=0,032). La obesidad tipo I (IMC>30 kg/m2 fue significativamente más frecuente en mujeres (29,2%) que en hombres (7,9%) (p=0,007) alcohólicos. Conclusiones: Las mujeres con dependencia alcohólica muestran elevada comorbilidad médica que las expone a desarrollar complicaciones orgánicas graves (AU)

Background and objective: To analyze gender differences in the hepatic, nutritional and metabolic complications associated with alcoholism. Patients and methods: Cross-sectional study in alcoholic patients admitted to detoxification in two university hospitals of Barcelona between 1999 and 2006. During admission, co-morbidity prior to admission was assessed and blood samples to analyze biological markers were collected. Demographic and anthropometric data, daily alcohol consumption and other drug use characteristics were also obtained at admission.Results: There were 566 admissions in 480 patients (375 males). Age at admission was 43years (IQR: 36.3-49.0years). Overall, 68.4% showed macrocytosis (MCV > 95 fl), 81.7% GGT>40 U/L and 57.7% AST>37 U/L. Regarding liver function tests, frequency of alkaline phosphatase > 120 U/L was significantly higher in women (18.5 vs 10.5%, p=0.037). However, the prevalence of hyperferritinemia (> 90 ng/mL) was significantly higher in alcoholic men (85.7% vs 62.2%) (p=0.000). Having multiple liver function test alterations was significantly higher in men (OR: 1.64, 95% CI: 1.01-2.65) (p=0.043). Women showed significant differences regarding the prevalence of macrocytosis (77.5% vs 65.8%, p=0.026), low serum creatinine (< 0.7mg/100mL) (28.2 vs 14.6%, p=0.001), low serum ferritin (< 30 ng/mL) (10.8 vs 3.9%, p=0.020), as well as of multiple nutritional alterations (OR: 1.59, 95% CI: 1.02-2.48) (p=0.040). However, men had higher prevalence of anemia than women (32.3 vs 21.4%, p=0.032). Prevalence of type I obesity (BMI>30kg/m2) was significantly higher in alcoholic women (29.2 vs 7.9%, p=0.007). Conclusions: Hepatic, nutritional and metabolic complications of alcoholism in women are frequent, thus increasing the risk of developing adverse clinical outcomes (AU)

[Gender and liver, nutritional and metabolic alterations of severe alcoholism: a study of 480 patients]. / Género y alteraciones hepáticas, nutricionales y metabólicas del alcoholismo grave: estudio de 480 pacientes.

BACKGROUND AND OBJECTIVE: To analyze gender differences in the hepatic, nutritional and metabolic complications associated with alcoholism. PATIENTS AND METHODS: Cross-sectional study in alcoholic patients admitted to detoxification in two university hospitals of Barcelona between 1999 and 2006. During admission, co-morbidity prior to admission was assessed and blood samples to analyze biological markers were collected. Demographic and anthropometric data, daily alcohol consumption and other drug use characteristics were also obtained at admission. RESULTS: There were 566 admissions in 480 patients (375 males). Age at admission was 43 years (IQR: 36.3-49.0 years). Overall, 68.4% showed macrocytosis (MCV > 95 fl), 81.7% GGT>40 U/L and 57.7% AST>37 U/L. Regarding liver function tests, frequency of alkaline phosphatase > 120 U/L was significantly higher in women (18.5 vs 10.5%, p=0.037). However, the prevalence of hyperferritinemia (> 90 ng/mL) was significantly higher in alcoholic men (85.7% vs 62.2%) (p=0.000). Having multiple liver function test alterations was significantly higher in men (OR: 1.64, 95% CI: 1.01-2.65) (p=0.043). Women showed significant differences regarding the prevalence of macrocytosis (77.5% vs 65.8%, p=0.026), low serum creatinine (< 0.7 mg/100mL) (28.2 vs 14.6%, p=0.001), low serum ferritin (< 30 ng/mL) (10.8 vs 3.9%, p=0.020), as well as of multiple nutritional alterations (OR: 1.59, 95% CI: 1.02-2.48) (p=0.040). However, men had higher prevalence of anemia than women (32.3 vs 21.4%, p=0.032). Prevalence of type I obesity (BMI>30 kg/m(2)) was significantly higher in alcoholic women (29.2 vs 7.9%, p=0.007). CONCLUSIONS: Hepatic, nutritional and metabolic complications of alcoholism in women are frequent, thus increasing the risk of developing adverse clinical outcomes.

Prevalence and routine assessment of unhealthy alcohol use in hospitalized patients.

OBJECTIVES: To determine the prevalence of alcohol misuse among medical inpatients and the methods used by medical staff to evaluate alcohol consumption. METHODS: Multicenter, prospective, observational, cross-sectional study performed at 21 hospitals in Spain. All adult patients hospitalized in internal medicine wards on 12 March 2008 were eligible for study. Alcohol consumption was evaluated with the Alcohol Use Disorders Identification Test (AUDIT-C and AUDIT) and the Systematic Inventory of Alcohol Consumption questionnaire. Drinking patterns were determined according to clinical evaluation using ICD-10 criteria. Medical records were reviewed to gather information on the recording of alcohol use. RESULTS: We assessed 1039 inpatients, of whom 123 (12%) had unhealthy alcohol drinking patterns. Alcohol misuse was more frequent among males (odds ratio 5.20), younger patients (odds ratio, 14.17), median age patients (odds ratio, 2.99), and South Region (odds ratio, 1.77). Alcohol use during hospitalization was recorded in 603 inpatients (59%); quantitative records were performed in 28% of hazardous and harmful drinkers and in 41% of dependent patients. Lack of alcohol use recording was more frequent among females (odds ratio 1.73), median and older age groups (odds ratios 1.44 and 1.73, respectively), Northwest Regions (odds ratios 3.46). Patients from the East Region (odds ratio 0.47) had more frequently assessed the question in their medical records. CONCLUSIONS: Prevalence of alcohol misuse was higher in hospitalized patients than in the general population. Adequate quantitative recording was infrequent. We stress the need to implement measures to increase and improve the detection and recording of alcohol use.

Genotypic and phenotypic resistance patterns at virological failure in a simplification trial with nevirapine, efavirenz or abacavir.

BACKGROUND: The NEFA Study was a randomized study comparing nevirapine (NVP), efavirenz (EFV) or abacavir (ABC) as substitutes for protease inhibitors in a large group of HIV-1-infected patients successfully treated with antiretroviral regimens containing protease inhibitors. OBJECTIVE: To evaluate genotype and phenotype resistance patterns among patients who have experienced virological failure under one of the three study arms. METHODS: Patients with virological failure, defined as two consecutive determinations of HIV-1 RNA > 200 copies/ml, were analysed for phenotypic susceptibility and HIV-1 mutations. RESULTS: Of the 460 patients included in the study, 51 (11%) experienced virological failure after 24 months of follow-up while on assigned study medication. A higher proportion of patients in the ABC [25 (17%)] than in the NVP [14 (9%)] or EFV [12 (8%)] arms selected resistance to the study drug (P = 0.04). Moreover, a much higher number of resistance mutations to one or more of the backbone nucleoside reverse transcriptase inhibitor drugs contained in the failing regimen were observed in the ABC than in the EFV or NVP arms. In general, there was a good concordance among genotype and phenotype resistance testing, except for ABC, stavudine and didanosine, where phenotypic resistance testing added valuable information (fold change in the median inhibitory concentration). CONCLUSIONS: Cross-resistance involving nucleoside reverse transcriptase inhibitor drugs might explain the higher risk of virological failure in patients switched to ABC-containing antiretroviral therapy. Phenotypic resistance testing may be helpful in interpreting unclear genotypic results.

Metabolic benefits 24 months after replacing a protease inhibitor with abacavir, efavirenz or nevirapine.

OBJECTIVE: To evaluate the 24-month metabolic and morphological benefits obtained from replacing the protease inhibitor (PI) in a regimen with nevirapine, efavirenz or abacavir. DESIGN AND METHODS: NEFA was a randomized study designed to compare the efficacy of nevirapine, efavirenz or abacavir as substitutes for PI. A subset of 90 patients [abacavir (n = 29), efavirenz (n = 32), nevirapine (n = 29)] formed the metabolic study. Fasting total cholesterol (TC), high density lipoprotein cholesterol (HDL-c) and triglycerides levels were determined. Glucose homeostasis parameters were also collected. Lipodystrophy was evaluated by clinical examination and morphological measurements. RESULTS: Treatment simplification led to overall lipid profile improvements. At 24 months, the two non-nucleoside reverse transcriptase inhibitors produced similar lipid benefits: HDL-c levels increased [efavirenz, 15% (P = 0.001); nevirapine, 21% (P < 0.001)] and TC to HDL-c ratios decreased [efavirenz, 14% (P < 0.001); nevirapine, 19% (P < 0.01)], an effect not observed in the abacavir arm. Non-HDL-c levels decreased by 10% in both the abacavir (P = 0.001) and efavirenz (P < 0.05) arms. Significant decreases in the levels of triglycerides occurred for the first year in all treatments; however, at 24 months most of the initial loss had been regained. Patients with baseline moderate or severe lipodystrophy obtained less-pronounced lipid benefits. Several insulin resistance markers showed a trend towards improvement. Conversely, no improvements in morphological abnormalities were observed. CONCLUSIONS: Replacing PI with efavirenz, nevirapine or abacavir improved the lipid profile, with more marked results in non-lipodystrophic patients. In contrast, this strategy does not seem to be effective for reversing body fat abnormalities.

Outpatient care compared with hospitalization for community-acquired pneumonia: a randomized trial in low-risk patients.

BACKGROUND: The Pneumonia Severity Index (PSI) has been advocated as an objective measure of risk stratification to help determine the initial site of treatment for patients with community-acquired pneumonia. OBJECTIVE: To determine whether outpatient care of PSI-defined low-risk patients with community-acquired pneumonia is as safe and effective as hospitalization. DESIGN: Unblinded, randomized, controlled trial. SETTING: 2 tertiary care hospitals. PATIENTS: 224 immunocompetent adults in risk class II or III (PSI scores